β-Adrenergic Blockade for Anthracycline- and Trastuzumab-Induced Cardiotoxicity

Abstract

Breast cancer is the second leading cause of cancer-related death among women in the United States.1 Approximately 25% to 30% of breast cancers have overexpression of human epidermal growth factor receptor 2 (HER2), which is associated with an adverse prognosis.2 Adjuvant chemotherapy with trastuzumab, the humanized monoclonal antibody that directly targets HER2, significantly improves disease-free and overall survival in these patients.3 However, trastuzumab, especially when given in combination with anthracyclines, has been associated with asymptomatic and symptomatic left ventricular (LV) dysfunction3 that can lead to premature discontinuation of trastuzumab therapy and significant cardiac morbidity. Article see p 420 In this issue of Circulation: Heart Failure , Seicean et al4 retrospectively evaluated the incidence of new symptomatic heart failure (HF) in patients with breast cancer treated with anthracyclines, trastuzumab, or both, at the Cleveland Clinic between 2005 and 2010. Using 1:2 propensity matching, they compared patients on continuous β-blockers during cancer treatment to those not on β-blockade, and assessed the effect of incidental β-blocker use on new symptomatic HF and noncardiac mortality during a median follow-up of ≈3 years. The results of this study show that trastuzumab, when given alone or in combination with anthracyclines, substantially increased the risk of symptomatic HF compared with anthracyclines alone (hazard ratio, 9.5; 95% confidence interval, 3.9–23.1). Furthermore, incidental β-blocker use significantly reduced the incidence of symptomatic HF (hazard ratio, 0.2; 95% confidence interval, 0.1–0.7) but did not affect noncardiac mortality in patients with breast cancer treated with trastuzumab, anthracyclines, or both. This article highlights 2 important issues: (1) it emphasizes the magnitude of trastuzumab cardiotoxicity in the real world, and (2) it provides support for the hypothesis that prophylactic β-blocker use may be cardioprotective in patients receiving trastuzumab, anthracyclines, or both. Anthracyclines cause a dose-dependent toxicity that is felt …